CONFORMATION OF 2 PEPTIDES CORRESPONDING TO HUMAN APOLIPOPROTEIN-C-I RESIDUES 7-24 AND 35-53 IN THE PRESENCE OF SODIUM DODECYL-SULFATE BY CD AND NMR-SPECTROSCOPY

Peptides corresponding to the proposed lipid-binding domains of human apolipoprotein C-I, residues 7-24 (ALDKLKEFGNTLEDKARE) and 35-53 (SAKM REWFSETFQKVKEKL), were studied by CD and two-dimensional H-1 NMR spect roscopy. Sodium dodecyl sulfate (SDS) was used to model the lipoprotei n environment. Analysis of the CD data shows that both peptides lack w ell-defined structure in aqueous solution but adopt helical, ordered s tructures upon the addition of SDS. The helical nature of the peptides in the presence of SDS was confirmed by H-alpha secondary shifts. A t otal of 199 (apoC-I(7-24)) and 266 (apoC-I(35-53)) distance restraints were used in distance geometry and simulated annealing calculations t o generate average structures for both peptides in aqueous solutions c ontaining SDS. The backbone (N, C-alpha, C=O) RMSD from the average st ructure of an ensemble of 20 structures was 0.73 +/- 0.22 and 0.48 +/- 0.14 Angstrom for apoC-I(7-24) and apoC-I(35-53), respectively. In th e presence of SDS, the distance geometry and simulated annealing calcu lations show that both peptides adopt well-defined amphipathic helices with distinct hydrophobic and hydrophilic faces. The calculated struc tures are discussed relative to predicted structures. Comparing our CD and NMR results for the apoC-I fragments in SDS with CD results of ot hers obtained in the presence of dimyristoylphosphatidylcholine indica tes that SDS may be a better model of the lipoprotein environment.